PHENYLKETONURIA

Know the condition,

choose the right nutrition

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TABLE OF CONTENTS PKU (Phenylketonuria)

What is PKU? 2What is Phenylalanine (Phe)? 3 How common is PKU? 3Potential PKU consequences 4How is PKU diagnosed? 4What is the clinical presentation? 5How is PKU treated? 6

PKU NUTRITIONAL GUIDE

Diet as therapy 6 – 7 Basic rules of the diet 8What are the recommended protein levels? 9Phenylalanine (Phe) in various foods 10-11PKU and a balanced diet 12Feeding babies with PKU 13 Feeding children with PKU 14 PKU in teenagers and adults 15PKU in pregnancy 16Dietary foods: How can they help? 17

PKU IN EVERYDAY LIFE

Tips and Tricks 18Aspartame beware! 19Traveling and eating out 19 – 20

ADVICE FROM YOUR DIETITIAN 21

Copyright 2016

Dr. Schar USA, Inc.

125 Chubb Ave

Lyndhurst, NJ 07071

USA

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WHAT IS PKU?PHENYLKETONURIA OR PKU IS THE MOST COMMON

CONGENITAL DISORDER AFFECTING THE METABOLISM

OF PROTEINS.

PKU is due to the mutation of a genethat codifies phenylalanine hydroxy-lase (PAH), the enzyme that metab-olizes the amino acid phenylalanine into tyrosine, another amino acid. The absence of phenylalanine

hydroxylase prevents this reaction,and may cause damage to the brain.If identified at birth, early treatmentallows normal development andprevents any compromise of thecentral nervous system.

WHAT IS PHENYLALANINE (PHE)?

HOW COMMON IS PKU?

AMINO ACIDS ARE THE BUILDING BLOCKS OF PROTEINS.

PHENYLALANINE IS AN ESSENTIAL AMINO ACID.

PKU HAS A FREQUENCY OF 1 IN EVERY 10,000 BIRTHS

AND IS ONE OF THE "RARE" GENETIC DISEASES.

This means that the body cannotsynthesize it and therefore must beprovided through foods. It is vital inorder to permit the synthesis of themost common essential proteins.

Normally phenylalanine is metabo-lized into tyrosine by phenylalaninehydroxylase. An intake of phenylala-ninecan only cause problems forthose affected by phenylketonuria.

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MOTHERHealthy Carrier

Healthy Child25%

Affected Child25%

Healthy Carrier50%

FATHERHealthy Carrier

PROBABILITY OF INHERITANCE

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POTENTIAL PKU CONSEQUENCES WHAT IS THE CLINICALPRESENTATION?

HOW IS PKU DIAGNOSED?

The genetic mutation results in a de-ficiency of the enzyme phenylalanine hydroxylase, which is responsible for metabolizing phenylalanine.A deficiency in this enzyme causesphenylalanine to accumulate in theblood, urine and tissues and thusresults in slower development of thecentral nervous system in the period

from birth until puberty, possiblyleading to neuromotor and psychicalretardation or premature death.The accumulation of phenylalaninemay also cause a lack of melanin,which may lead to very fair skin.For this reason, those with PKU,if left untreated, have very fair skinand blue eyes.

In a healthy person who is not affected by PKU, the level of phenylalanine in the blood will not exceed 2 mg per deciliter of blood. Nor will healthy bearers of the defective gene exceed this 2 mg per deciliter limit, although they will have difficulty metabolising phenylalanine.

Hyperphenylalaninemia (elevated levels of Phe in the blood), occur when the values of phenylalanine in the blood on an unrestricted diet exceed the level of 2 mg per deciliter of blood, but are less than 6 mg per deciliter. To determine how much phenylalanine can be tolerated in the diet of those with PKU, there are three distinct levels identified based on blood tests.

Given the serious consequences thatpeople with PKU may encounter, all babies in the USA and Europe are now tested for the condition. Neonatal screening in the first 42 to 72 hours of life permits the early diagnosis of PKU and other congenital metabolic diseases. This allows apropriate treat-ment to be undertaken timely, thus preventing any damage to the brain.

Analysis can be performed via the Guthrie test (a drop of blood is taken from the baby’s heel and exposed to a bacterium) or more moderntechniques, such as tandem massspectrometry. It is also possible toperform prenatal diagnosis for at-risk pregnancies, for example in familieswhere one or more children areaffected by PKU.

MILD PHENYLKETONURIA (HYPERPHENYLALANINEMIA):

the values of phenylalanine in the blood on an unrestricted diet arebetween 60 µmol/l and 10 µmol/l.

MODERATE PHENYLKETONURIA (PKU):

the values of phenylalanine in the blood on an unrestricted diet arebetween 10 µmol/l and 20 µmol/l.

CLASSICAL (OR SEVERE) PHENYLKETONURIA (PKU):

the values of phenylalanine in the blood on an unrestricted diet are over20 µmol/l. Enzymatic activity is less than 5%.

Alternative therapies, such as genetictherapy, are still at the experimentalphase. A correctly managed dietregime will ensure a balanced nutrient intake and normal development of the tissue and nervous systems.

The dietary treatment of phenylke-tonuria is based on a diet that is lowin phenylalanine.

Therefore the diet limits its con-sumption both from natural sources (proteins) and artificial sources (additives). In order to prevent the functional and structural damage caused by an accumulation of this amino acid the diet must also ensure the adequate consumption of the amino acids essential for growth.It is therefore necessary to take dietary supplements (amino acid mixtures) with a balanced content of amino acids (excluding Phe), mineral, vitamins and trace elements.

Research into nutrition has made enormous progress and people with PKU can now obtain numerous products with a very low protein content (protein-free products), such as pasta, bread, flour, cookies, crackers and milk. These replace normal products and allow the daily menu to be varied, as well as provid-ing an adequate number of calories and other nutrients.

In this way the metabolic condition can be solved and the intermediate accumulation of toxic levels can be avoided.

Finally, the effectiveness of dietary therapy can be controlled via constant monitoring of the metabolic balance, physical growth parameters based on age) and the psychomotor develop-ment. The nutritional indicators are also constantly controlled to avoid any nutrient imbalance or deficit.

HOW IS PKU TREATED?

THE DIET AS THERAPY

EARLY DIAGNOSIS AND A STRICT DIET CAN PREVENT

THE ONSET OF THE SYMPTOMS OF PHENYLKETONURIA.

ADHERENCE TO THE DIET MUST BE CONSTANTLY MONITORED

AND ITS BENEFITS TESTED BY REGULAR MONITORING

OF THE PLASMA LEVELS OF PHENYLALANINE.

DIET THERAPY HISTORICALLY HAS BEEN THE MAIN THERAPY

USED IN THE MANAGEMENT OF NUMEROUS CONGENITAL

METABOLIC PATHOLOGIES, INCLUDING PHENYLKETONURIA.

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LIFELONG STRICT ADHERENCE TO THE DIET

Until recently it was considered sufficient to follow this nutritional therapy until puberty, today many experts suggest maintaining this set diet for the rest of one’s life. There is substantial evidence to continuethe diet for life. Abandoning the low protein diet as an adult will increase the risk of lowering IQ level. There exists however a benign form of PKU that does not require treatment and is compatible withnormal eating (benign hyperphenylalaninemia).

In some cases, in the so called "BH4 responders" a pharmaco-logical treatment with BH4 can be applicated. As conseguence the Phe tolerance increases and the diet can be less strict.

BASIC RULES OF THE DIETTHE DIETARY REGIME HAS SOME GROUND RULES.

MOST IMPORTANT IS TO KEEP THE CONCENTRATION OF

PHENYLALANINE WITHIN SAFE LIMITS.

WHAT ARE THE RECOMMENDEDPROTEIN LEVELS?

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This requirement is slightly higherthan for the general population,because of the lower nutritive qualityof the amino acids contained in thesupplements compared to theproteins naturally found in food.

Most protein requirements (approx-imately 80%) are covered by aminoacid mixtures, with only 20% coming from protein-free natural foods and products.

A LOW-PROTEIN DIET MUST NEVERTHELESS MEET

INDIVIDUAL PROTEIN NEEDS: THESE VARY WITH AGE

AND FLUCTUAT E BETWEEN 1 AND 3 GRAMS OF PROTEIN

PER KILO OF BODY WEIGHT PER DAY.

All natural proteins contain 4-6%phenylalanine and it is not thereforepossible to meet the body’s proteinrequirements without exceeding itsphenylalanine needs.

• Foodstuffs with a high protein content, such as meat, fish, eggs, cheese, soy and nuts are not recommended for those with classic phenylketonuria.

• Natural foods that are low in pro-tein, such as fruit and vegetables are recommended as the base of the diet regime.

The necessary calories and energyare then provided by protein-freefoods such as flour, bread and pasta.

The dietary regime must limit thephenylalanine intake and satisfy therequirements in terms of essentialamino acids while avoiding anyexcessive quantities. Finally, theremust be adequate vitamins, minerals,carbohydrates, essential fatty acidsfor the persons age, sex and energyneeds and to prevent malnutritionproblems. It is therefore stronglyrecommended to take amino acidsupplements consisting mainly ofmixtures of L-amino acids, vitaminsand mineral salts. The diet must allowfor normal growth and development,while avoiding the accumulation ofphenylalanine.

=

RIC

H

TO HIGH IN

Phe

20%• Fruits and vegetables

• Low-protein diet products

80%• Amino acid

mixtures

LOW PROTEIN PASTA

LOW PROTEIN CROSTINI

PKUDRINK

LOWPROTEIN

BREAD

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PHENYLALANINE (PHE)IN VARIOUS FOODS

THE FOODSTUFFS/DRINKS AT

THE BASE OF THE PYRAMID

ARE THE FOUNDATION OF THE

NUTRITION IN PKU. THE HIGHER

A PRODUCT IS ON THE PYRA-

MID THE SMALLER THE DAILY

CONSUMPTION-QUANTITIES

SHOULD BE.

P D

WaterWater

Fruit and low-protein vegetables

Beverages

Mais

Sweets

Butter

Amino acid mixtures

PKUDRINK

Protein-rich vegetables

Milch Milch

Reis

Low-protein diet foodstuffs Oil

Protein-rich foodstuffs

Milk Milk

LOW PROTEIN PASTA

W PROTEIN PASTA

LOW PR PASTA

LOW PROTEIN CROSTINI

W PROTEIN ROSTINI

WaterWater Water WaterWater Water

P D

AMINO ACID MIXTURES

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PKU AND A BALANCED DIET

Generally, two methods are usedto monitor the phenylalaninerequirements and the blood levels.

• The first method centers on the everyday total quantity of phenylalanine, by calculating the phenylalanine content in the main foods consumed each day.

• The second method is instead based on the concept of equivalents, with the calculation criterion varying around the world. An equivalent corresponds to a quantity of between 10 and 50 mg of phenylalanine. For example, 1 equivalent (20 mg of phenylala-nine) = 50 g of carrots.

Foods are subdivided into categories on the basis of the calculation

of equivalents: fruit/vegetables and cereals. The cereals category includes commercially available protein-free or low-protein foods. The categories are balanced out and subdivided throughout the day. Every method has its pros and cons, but both seem to adequately control the concentrations of phenylalanine in the blood.

Finally, to check that nutrition is properly balanced, the levels of phenylalanine in the blood must be monitored regularly. This is done by taking a small blood sample and putting a drop onto absorbent paper.

BLOOD TESTS DONE AT BIRTH CAN IDENTIFY THE AMOUNT

OF PHENYLALANINE AN INDIVIDUAL CAN TOLERATE.

THE PHE TOLERANCE WILL BE ADJUSTED CONTINUOUSLY

TO THE INDIVIDUAL METABOLIC SITUATION.

THE DIET SHOULD THEN BE INDIVIDUALIZED TO INCLUDE A

VARIETY OF FOODS WITH THE CORRECT AMOUNT OF PHE

THROUGH OUT THE DAY.

Mother’s milk, as well as providingamino acids and essential fattyacids (mainly Omega 3 with neuroprotective effects), also contains small amounts of phenylalanine. Immediately following diagnosisthe daily levels of Phe must first bereduced to within the safe range.Breast-feeding for babies affected

by PKU is therefore encouraged andhelps create a strong tie betweenmother and child. Breast-feedingmust subsequently be supplementedwith appropriate amino acid mixtures.Finally, the levels of phenylalanine inthe baby’s blood must be regularlymonitored.

FEEDING BABIES WITH PKUWHERE PHENYLKETONURIA IS DIAGNOSED AS A RESULT

OF NEW BORN SCREENING, IT IS IMPORTANT TO BEGIN

DIETARY TREATMENT IMMEDIATELY.

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This dietary approach depends onthe child’s tolerance (i.e. the formof phenylketonuria present). A diettotally lacking in protein would resultin inadequate growth. There must beadequate provision of the right aminoacids to keep the child healthy andensure growth. This can be achievedthrough supplementary mixtures ofamino acids that do not containphenylalanine and are age appropriate.It is also important to pay attention toa balanced intake of vitamins (aboveall vitamin D, vitamin A, vitamin B12), mineral salts (calcium), essential fatty acids (Omega 3) and micronutrients (selenium, zinc, iron).

Depending on the phenylalaninecontent tolerated by the child, the

protein requirements can be met bymeans of mixtures of amino acids andnatural proteins (foods). For classicalphenylketonuria, for example, 350 mgof phenylalanine a day corresponds toapproximately 6 g of proteinfrom foods.

The caloric requirements must beage appropriate. However, becauseof the dietary restrictions, may beinsufficient. This could compromisegrowth while prompting the catabo-lism of proteins from muscle andcause the release of phenylalanine.

The diet adherence and affectivenessshould be monitored by taking a blood sample each week to check the levels of phenylalanine.

There must therefore be a balance between the minimumpossible amount of phenylalanine while meeting their protein and energy requirements. The first step is to prevent the accumulation of phenylalanine. This does not mean a total absence of phenylalanine. It is unnecessay to exclude all foods containing protein; it is advisable to provide foods with a moderate protein content that are however low in phenylalanine.

FEEDING CHILDREN WITH PKUCHILDREN ARE GROWING AND HAVE HIGH

CALORIE AND PROTEIN REQUIREMENTS.

Adult requirements for amino acidsare not significantly different fromthose of children, but there are someother, equally important, nutrients.

These include:

• calcium and vitamin D to prevent osteoporosis (loss of bone mass)

• folic acid to prevent arteriosclerosis (hardening of arterial walls)

• fiber, for normal digestive health

• Omega 3 essential fatty acids which strengthen immunity and have neuroprotective effects

The amino acid mixtures for tee-nagers and adults are available inpractical packaging that allows foran active lifestyle.

Testing of phenylalanine in the bloodis less frequent than for infants, butregular monthly monitoring is stillnecessary.

PKU IN TEENAGERSAND ADULTSTHE RIGHT DIET PERMITS THE REGULAR DEVELOPMENT

OF ADOLESCENTS, BOTH MENTALLY AND PHYSICALLY,

ALLOWING THEM TO LEAD NORMAL LIVES.

Phe levels should be closely monitored. Home blood test results should be routinely reviewed at clinic visits.

DIETARY FOODS:HOW CAN THEY HELP?At the same time, however, otheramino acids, vitamins and mineralsand calories must be provided toensure the individual has adequatenutrition. Dietary products with a low

NUTRITION FOR THOSE WITH PHENYLKETONURIA MUST BE

LOW IN PROTEIN AND ABOVE ALL LOW IN PHENYLALANINE.

protein content meet this aim and arespecifically designed for those whomust follow a low-protein diet.There are two types of product:protein-free foods with a proteincontent of less than 1% and low- protein foods with a protein contentof between 1% and 2%. Protein-freeproducts make it easier to follow alow-protein diet and provide varietyin the diet.

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PKU AND PREGNANCY THE DESIRE TO HAVE CHILDREN IS THE MOST NATURAL

IMPULSE IN THE WORLD. FOR WOMEN WITH PKU, CONSTANT

AND RIGOROUS ATTENTION IS REQUIRED FROM THE INITIAL

“DECISION” TO HAVE A CHILD.

A strict diet is necessary even beforeconception in order to keep the concentration of phenylalanine within the desired limits. Ideally, in the six months before conception, a level of phenylalanine in the blood of (120 µmol/l) should be achieved and maintained.

Foods that should be cut out com-pletely are all products of animal origin (meat, fish, eggs, milk and dairy products in general) and beans. Grain-based foods (bread, pasta and bakery products) as well as eggs and milk can be substituted with protein- free dietary products.

Women with PKU whose children are born without the disease can breastfeed their babies, even though their milk is richer in phenylalanine than milk from a healthy mother. The

diet must be maintained for life and routine blood testing will be required to establish that nutritional intake is balanced. The greater the motivation to follow a strict, rigorous diet, the greater its success in ensuring that a child will not face any consequences (e.g. mental retardation) of the mother’s phenylketonuria.

The levels of phenylalanine in theblood must be reduced before preg-nancy and held stable at 120 µmol per liter blood. If, prior toconception, the blood level of pheny-lalanine in the mother-to-be is fullycontrolled, i.e. less than 240 µmol per liter blood, the child has optimum conditions for normal development and, in most cases (as the probability is minimal), the unborn baby will not be affected by phenylketonuria even if it is a carrier of the altered gene.

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ASPARTAME – BEWARE!

TRAVELING ANDEATING OUT

ASPARTAME IS AN AUTHORIZED FOOD ADDITIVE WHICH

CONTAINS PHE.

PKU IS NOT AN OBSTACLE TO TRAVELING.

It is an artificial sweetening agent and flavour enhancer that is used in foodssuch as drinks, bakery products and sweets, dairy products, chewing gum and weight loss products.

Aspartame consists of two amino acids, phenylalanine and aspartic acid, and should thus should be avoided by those with PKU.

Careful travel planning should includeobtaining information on the placesto be visited, including whether thereare PKU treatment centers, checkingfor shops that carry low proteinproducts, packing enough amino acidmixtures and low protein productsfor your stay.

TIPS AND TRICKSA LOW PHE DIET REQUIRES CLOSE ATTENTION TO DETAILS.

HERE ARE A FEW TIPS TO HELP:

As pheynlalalnine tolerance varies in each individual, there is not a one size fits all treatment plan.Even though the diet must be cus-tomized to each person, there are some general rules for everyone:

• Foods are in general weighed after they have been peeled or trimmed and before cooking. The edible part means that part of the food that is peeled or trimmed and ready to be cooked (or consumed raw).

• The phenylalanine and protein content of each food is calculated on the basis of various tables showing the composition of the foods.

• Where possible, the exact content of phenylalanine and protein is also calculated for those foodstuffs (fruit and vegetables) that are notable for their low phenylalanine content.

• The ingredients in the recipes, inpar-ticular the amount of protein-freefoods, can be adapted to personal requirements.

• Milk can be replaced with low- protein milk.

• Eggs can be substituted (egg substitute).

• The presentation of a dish is impor-tant; attractively presented food is more inviting.

• The amount of salt or sugar, if not specified, may be adjusted to taste.

• Herbs, as well as vinegar and spices, are optional and can be added to taste, but they have to be taken into account when calculating the Phe-content.

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When travelling abroad it may beuseful to carry a diagnosis issued byyour own hospital/doctor/PKU centeron letterhead that also gives a list ofall special products and the reasonthey must be carried: this will not only speed up customs procedures but will also ensure that suitable treatment is received if necessary.

A small scale will be useful, as willsome resealable containers in whichto keep the foods or protein mixes.It is important to maintain the intakeof supplements. It may be helpful topack protein mises and supplementsin single servings. This ensures properdistribution of protein and amino acids over the day and allows for ease of preparation while traveling. Finally,it is useful to keep a diary of yourfood intake for the day to record howmuch phenylalanine you consume.

Contact your hotel before hand toarrange for a refrigerator or a smallkitchenette to allow for preparationand storage of foods.

When flying it is recommended toselect the plain vegetarian menuoption. It’s a good idea to inquire about the methods used in other countries for measuring phenylala-nine in the blood and to learn the key phrases in the local language. Bring your prescription and diagnosis with you as this may allow you extra weightfor your checked days.

Be sure to carry at least 1-2 dayssupply of your foods and supplementsjust in case your bags get delayedor lost.

ADVICE FROM YOUR DIETITIAN

The new LOW-PROTEIN line

for nutrition therapy for

PHENYLKETONURIA (PKU)

info.us@mevalia.com www.mevalia.com

All MEVALIA low protein products can be

ordered conveniently from home.

Visit our online shop: shop.mevalia.com

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Lyndhurst, NJ 07071

USA

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